With the advent of combinatorial library methods for generating large libraries of compounds, there has been a growing interest in high-throughput screening (HTS) methods for screening such libraries.
The most widely used HTS screening method involves competitive or non-competitive binding of library compounds to a selected target protein, such as an antibody or receptor. Thus, for example, to select a library compound capable of blocking the binding of a selected agonist to a receptor protein, the screening method could assay for the ability of library compounds to displace radio-labeled agonist from the target protein.
Although such binding assays can be used to rapidly screen large numbers of compounds for a selected binding activity, the assay itself may have limited relevance to the actual biological activity of the compound in vivo, e.g., its ability to interact with and affect the metabolic behavior of a target cell.
It would therefore be useful to provide high throughput screening methods capable of testing the effects of large numbers of library compounds on target cells of interest.